What is the recommended dose of terlipressin for Hepatorenal Syndrome (HRS)?

From the Guidelines

The recommended dose of terlipressin for Hepatorenal Syndrome (HRS) is 1 mg intravenously every 4-6 hours, which can be increased to a maximum of 2 mg every 4-6 hours if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value, as per the most recent guidelines 1.

Key Considerations

• The dose of terlipressin should be adjusted based on the patient's response to treatment, with a maximum total daily dose of 12 mg/day 1.
• Terlipressin can also be administered by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d, or reversal of HRS 1.
• Patients on terlipressin require close monitoring for potential side effects, including ischemic complications, abdominal pain, diarrhea, and cardiovascular complications, including arrhythmias and myocardial ischemia 1.
• Predictors of response to terlipressin treatment include markers of better liver function, better kidney function, an increase in the mean arterial pressure (MAP) of ≥ 5 mm Hg with treatment, and lower grades of acute-on-chronic liver failure (ACLF) 1.

Administration and Monitoring

• Terlipressin should be administered alongside albumin, typically given as 1 g/kg on day 1 followed by 20-40 g daily 1.
• Before initiating therapy, patients should be evaluated for contraindications, including severe cardiovascular disease, ischemic conditions, or pregnancy 1.
• During treatment, patients require close monitoring for potential side effects, and the decision to transfer to a higher level of care should be made based on clinical judgment 1.

From the FDA Drug Label

The pharmacokinetic parameters of terlipressin and its major active metabolite, lysine-vasopressin, were derived from population pharmacokinetic modeling with sparse PK samples from 69 patients with HRS-1. Following a 1 mg IV injection of terlipressin acetate, the median Cmax, AUC24h and Cave of terlipressin at steady state was 70.5 ng/mL, 123 ng×hr/mL and 14. 2 ng/mL, respectively.

The recommended dose of terlipressin for Hepatorenal Syndrome (HRS) is 1 mg IV injection every 6 hours, as mentioned in the context of the pharmacokinetic parameters and the effect of terlipressin on QTc interval in patients with HRS-1 2.

• The dose is administered intravenously.
• The dosing interval is every 6 hours.
• The maximum effect on blood pressure and heart rate occurred at 1.2 to 2 hours post dose.

From the Research

Dose of Terlipressin in HRS

• The recommended dose of terlipressin for Hepatorenal Syndrome (HRS) is initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there is no response 3.
• Terlipressin can be administered by intravenous infusion, with the dose adjusted based on the patient's response to treatment 3.
• The use of terlipressin in HRS has been shown to be effective in improving renal function and reducing mortality, with a significant increase in mean arterial pressure and systemic vascular resistance 4.
• The improvement in hemodynamics with terlipressin is associated with an increase in glomerular filtration rate and deactivation of the vasoconstrictor and sodium-conserving hormones, resulting in increased natriuresis 4.

Administration and Efficacy

• Terlipressin can be administered as a bolus or continuous infusion, with continuous infusion allowing for a lower daily dose and equal efficacy with fewer side effects 5.
• The response to terlipressin in randomized controlled trials was defined as a repeat reduction of serum creatinine to less than 1.5 mg/dl, with newer studies likely to require a response to treatment defined as a repeat serum creatinine to be less than 0.3 mg/dl from baseline 5.
• Terlipressin use is associated with ischemic side effects and potential for respiratory failure development, requiring careful patient selection and close monitoring 5.

Comparison with Other Treatments

• Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 3, 6.
• Norepinephrine plus albumin is also more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 6.
• The cost-effectiveness of terlipressin for HRS has been evaluated, with terlipressin plus albumin associated with lower total costs and a lower cost per complete response achieved compared to norepinephrine plus albumin and midodrine/octreotide plus albumin 7.